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BACKGROUND: Gorham-Stout disease (GSD) is a rare lymphatic disorder which results in bone destruction. Defects of the skull base are difficult to manage, we describe cases to better understand the disease and discuss treatment. METHODS: Retrospective study including all patients treated for GSD skull-base defects. Medical records, clinical, imaging and treatment data were studied. A systematic review of the literature included case reports of the diseases for further analysis. RESULTS: 6 patients (5 males, 1 female) were included. Mean age at diagnosis was 3.5 years (range 0-10). Follow-up was of 5.2 years. Patients were divided into Naso-temporal (NT) and Vertebro-temporal (VT) groups following anatomical location. NT patients (4 patients) all had petrous defects extending anteriorly, including sphenoid, ethmoidal and mandibular defects. They all had cerebro-spinal fluid leak (CSF) and recurrent meningitis (range from 3 to 7). Two of those patients had sequelae including deafness, paralysis and epilepsy. VT patients (2 patients) all had temporal, occipital bone and cervical vertebrae defects. None had CSF leaks but both died from medullar compression (preceded by tetraparesis in one case). Overall, five out of six patients had type I Chiari malformation. Interferon seemed to be the most efficient medical treatment. Surgery included petrectomy, endonasal surgery for CSF leak management and neurosurgery for medullar management but could not guarantee long-term effects. CONCLUSION: Main issues in skull base defects are CSF leaks and medullar compressions. Surgical treatment is necessary in both cases but can only be satisfactory if general medical treatment can stabilise the disease.

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INTRODUCTION: Desmoid-type fibromatosis (DF) is a rare benign lesion known for its local aggressiveness. The tumor management still remains under debate. Primary head and neck (HN), represents the second most prevalently affected sitein children with DF. This study aims to analyze the specificity of HN-DF in children, focusing on long-term effects of the tumor and therapies. METHODS: This retrospective multicenter study analyzed children treated for a HN-DF between 1993 and 2013. All medical files were reviewed and their outcomes analyzed according to the initial therapies provided. RESULTS: Sixteen children were selected. Mandibular and submandibular areas were the main locations (11 cases). Eight children underwent chemotherapy as first-line therapy with tumor control in 3 cases and 5 cases needing additional treatment. Six children underwent primary surgery: isolated in 3 cases and with additional treatment after tumor progression in 3 cases. A wait-and-see attitude was adopted for 2 children without any additional treatment in 1 case, and followed by additional chemotherapy in the other case. Total burden of treatment to control the disease was a biopsy (1 case), surgery (3 unique cases, 1 multiple case), surgery with chemotherapy (6 cases), and exclusive medical therapies (5 cases). Surgical postoperative sequelae were facial palsy (cases of parotid gland affection), XIth cranial nerve sacrifice or sensory impairment. CONCLUSION: HN-DF is a local and extensive disease that is difficult to control with surgery alone. Sequelae are frequent due to the initial tumor location or therapies. Initial conservative strategies need to be discussed in a multidisciplinary way in order to try to control the disease with the minimal morbidity.

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PURPOSE: The purpose of this work was to determine the epidemiology and the predictive factors of success of the surgical management of fourth branchial anomalies. METHODS: This is a multicentric retrospective review from 1998 to 2016 of patients who presented with an endoscopically-confirmed fourth branchial pouch anomaly. Data were analyzed according to sex, age, clinical features, number of recurrences, treatment modalities (endoscopic and/or cervicotomy), post-operative complications and follow-up. RESULTS: Fifty-two children have been included. The average age at diagnosis was 4.5â¯years. Among them, 73.1% were female, 11.4% were neonatal forms; 94.2% of lesions were left-sided; 75% of patients presented a cervical abscess as first symptom, and 7.7% of children presented with dyspnea. Average time between first symptoms and management was 9.5â¯months. Management was endoscopic in 73.1% of patients (laser in 84.2%, coagulation in 15.8%) with about a third of recurrence after one procedure. Overall success of endoscopic procedures reached 84.2%. A cervical open surgery was performed in 26.9% as first line treatment. Overall success of cervicotomy reached 85.7%. No complications of endoscopic surgery have been identified. There were 35.7% complications of cervicotomy (2 recurrent nerve palsy, 2 keloid scars, 1 pharyngostoma). An association was proved between recurrences and initial abscess (ORâ¯=â¯2.44), and with age between 3 and 5 (ORâ¯=â¯4). CONCLUSION: Endoscopic treatments appear to be effective in first line approach in the management of fourth branchial anomalies, offering an excellent efficiency with rare complications. We identified two risk factors of recurrence: age between 3 and 5â¯years old and history of cervical abscesses. LEVEL OF EVIDENCE: IV.

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Reunion Island is a French oversea department in the Indian Ocean with 1.6/1000, an estimated prevalence of deafness that is almost double as compared to the mainland France. Twelve children having isolated bilateral prelingual profound deafness along with motor delay attributed to vestibular areflexia were enrolled. Their mean walking age was 19 months. Electroretinography and temporal bone CT-scans were normal in all cases. A novel homozygous frameshift lipoma HMGIC fusion partner-like 5 (LHFPL5) variant c.185delT p.(Phe62Serfs*23) was identified using whole-exome sequencing. It was found in seven families. Four patients from two different families from both Reunion Island and mainland France, were compound heterozygous: c.185delT p.(Phe62Serfs*23) and c.472C > T p.(Arg158Trp). The phenotype observed in our patients completely mimics the hurry-scurry (hscy) murine Tmhs knock-out model. The recurrent occurrence of same LHFPL5 variant in Reunion Island is attributed to common ancestor couple born in 1693.

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Platinum is extensively used in the treatment of several childhood cancers. However, ototoxicity is one of the most notable adverse effects, especially in children. Several studies suggest that genetics may predict its occurrence. Here, polymorphisms associated with platinum-induced ototoxicity were selected from the literature and were investigated in a pediatric population treated with platinum-based agents. In this retrospective study, patients treated with cisplatin and/or carboplatin were screened. The patients with pre- and post-treatment audiogram (Brock criteria) available were included. We selected polymorphisms that have previously been associated with cisplatin ototoxicity with a minor allele frequency ≥30%. Deletion of GSTM1 and GSTT1, rs1799735 (GSTM3), rs1695 (GSTP1), rs4880 (SOD2), rs2228001 (XPC), rs1799793 (XPD) and rs4788863 (SLC16A5) were investigated. Data of one hundred and six children matching the eligible criteria were analyzed. Thirty-three patients (31%) developed ototoxicity (with a Brock grade ≥2). The probability of hearing loss increased significantly in patients carrying the null genotype for GSTT1 (P = 0.03), A/A genotype at rs1695 (P = 0.01), and C/C genotype at rs1799793 (P = 0.008). We also showed an association of the cumulative doses of carboplatin with cisplatin ototoxicity (P <0.05). To conclude, deletion of GSTT1, rs1695 and rs1799793 may constitute potential predictors of platinum-induced ototoxicity.

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The acoustic reflection method (ARM) is a non-invasive technique which uses the reflection of acoustic waves to measure the cross sectional area of nasal cavities in adults and patency of endotracheal tubes. Characteristics and volume of normal nasal cavities in pre-school children has so far not been studied. OBJECTIVE: The aim of this study was to determine the optimal ARM recording and the minimal cross-sectional area (MCA) and volume (NV) values in healthy children. DESIGN: Prospective monocentric study using the ARM in pre-school children (<6 years of age). RESULTS - DISCUSSION: Seventy children (age 2 to 5) were included in the study. Reliable measures were difficult to obtain in children younger than 2 years of age. The use of a standard nosepiece and a single-use surgical filter enabled reliable, serial recordings. Mean MCA values were 0.46, 0.53 and 0.58â¯cm2 in the 24-35, 36-47 and 48-60 months-old age groups, respectively. Mean NV values were 2.14, 2.59, and 2.86â¯cm3 in the same age groups. The MCA and NV values were significantly correlated with height, age and weight. In conclusion, the ARM is feasible in children over the age of 2 and seems to be a promising non-invasive tool to study the nasal cavity patency, anatomy, and volume.

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OBJECTIVE: Unilateral sensorineural hearing loss (USNHL) is known to impact on school performance and social skills during childhood, but the etiologies remain unclear. The aim of this study was to assess various etiologies and to study the clinical contexts in this population. METHODS: The study is a retrospective review. Characteristics of hearing loss (HL), audiometric parameters, imaging, and genetic and medical contexts were analyzed. RESULTS: Eighty children were included. USNHL was profound in 68%, could be progressive in 19%, and become bilateral in 7.5% of cases. Inner ear malformations were identified in 41% of cases; cochlear nerve deficiency (CND) was frequent (33%). Cytomegalovirus (CMV) infection and genetic syndromes were confirmed in 10 and 6% of cases, respectively. CONCLUSION: Long-term hearing follow-up remains useful in USNHL as it can become bilateral. Looking to etiology, MRI should be the gold standard, as CND is frequently observed and screening for CMV infection should be systematic. Genetic etiologies appear to be different compared to bilateral HL. Further genetic research in this domain is needed.

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OBJECTIVE: To analyze clinical signs and better define the underestimated long-term pain after implantation, to discuss etiological hypothesis, and to propose our department treatment algorithm and results. STUDY DESIGN AND SETTING: Retrospective review of children implanted with complaints of atypical pain in the area of device implantation, not in the immediate postoperative period, more than or equal to 4 on the Visual Analog Pain Scale (VAPS: 0-10) in the ENT pediatric department of Trousseau and Necker Enfants Malades Hospitals between 1998 and 2015. PATIENTS: All patients had full clinical and electrophysiological checking, and had normal functioning device. Exclusion criteria were: related history of local trauma, ongoing skin infection, magnet displacement, and device failure. INTERVENTION(S): Treatments and outcomes were reviewed, with a minimum of 6 months follow up. Two groups were analyzed: Group PS: pain associated with local swelling (nâ=â9) and Group P: isolated pain (nâ=â11). The first-line treatment was medical. In Group PS, anti-inflammatory, pain medication, and antibiotics were used at the same time; in Group P, only anti-inflammatory and pain medication was used. MAIN OUTCOME MEASURE(S): Success was defined when complete resolution of pain and swelling (pain scaleâ=â0). RESULTS: Twenty cases out of the 1,448 implanted patients in our department (1.4%) were included. Average age at first occurrence of pain was 15 years (3-22 yr). Mean delay between surgery and pain complaint was 5.8 years (0.25-14). Mean follow up was 2 years (0.5-5 yr).First line medical treatment was successful in eight cases (40%). Of the 12 patients who failed medical treatment and required surgery, two had resolution of pain with magnet change and 10 had resolution with reimplantation. (5/9 patients in Group PS and 7/11 in Group P).Microbiology was performed in 10/20 cases and analysis of explanted devices was performed in 7/10 cases. Positive microbiological culture of soft tissues was positive for 3/10 cases, biofilm was positive for 5/7 cases.Pain in the area of the implanted device can occur shortly after surgery or on long-term follow up. It has been seen in all device types. Pain may be clinically underestimated, as low VAPS grade (<5) or intermittent pain may be not reported. Low-grade infections might be a hypothesis to explain these pain. Management may include medical or surgical intervention. CONCLUSION: Pain in the implanted area can be a major complication leading to implant non-use. Rate may be underestimated because of the lack of medical report. At explantation, we recommend systematic evaluation of biofilm and device failure regardless of the suspected etiology of the pain.

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INTRODUCTION: Velopharyngeal insufficiency (VPI) is usually managed, besides speech therapy, by performing a velopharyngoplasty. An alternative approach is autologous fat grafting (AFG) of the posterior pharyngeal wall. About 5% of the population has internal carotid arteries (ICA) with an aberrant course. This anatomic variation can be responsible for surgical difficulties while when performing a velopharyngoplasty, and therefore lead surgeons to only consider a speech reeducation of VPI. However, AFG is does not bear such surgical morbidity. OBJECTIVE: The aim of this study is to retrospectively determine AFG efficiency on VPI in patients with aberrant ICA's courses who cannot benefit from a velopharyngoplasty, by comparing pre- and postoperative Borel Maisonny score (BMS) and intelligibility (Intell). METHODS: We conducted a retrospective study in 2 centers, including children with VPI and aberrant ICA's courses who underwent an AFG of the posterior pharyngeal wall from 2004 to 2015, in addition to speech therapy. RESULTS: Nine patients (4-11 years old) underwent the surgical procedure, 8 of them presenting a 22q11 microdeletion. All improved their VPI by AFG of the pharyngeal wall according to BMS and Intelligibility after a 10 months follow-up. The effect was stable after 3 years of follow-up. No severe complication (apnea, vascular injury) occured. CONCLUSION: AFG of the pharyngeal wall, associated with speech therapy, seems to be a safe procedure for patients with VIP and aberrant ICA's courses. Multiple procedures are possible if needed.

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OBJECTIVE(S): To describe a new and more simple surgical procedure for implanting the Vibrant Soundbridge (VSB) on the short process of the incus in children with ear atresia and atretic plate and present the audiometric results. METHODS: Since 2014, pre- and post-operative audiometric tests with tonal and vocal audiometryat the maximal follow up, respectively 33, 22 and 12 months were performed after VSB implantation at the ENT department, Necker Enfants Malades Hospital, Paris, France. 3 children aged 11, 9 and 15 years with conductive hearing loss due to high grade ear atresia and absent ear canal were implanted. The malformed and fused malleus-incus complex was found to be immobile in two of the subjects, who then underwent a superior tympanotomy to carefully remobilize the malleus. Stapes were mobile in all cases. The FMT clip was customized and crimped on the short process, stabilized by the metallic wire. RESULTS: At the maximum follow-up time, the bone conduction was unchanged, and the mean aided ACPTA was 21 dB, 29 dB and 30 dB, compared to 66 dB, 63 dB and 68 dB unaided, respectively. The word recognition score (WRS) at 65 dB SPL increased from 10%, 10% and 70% (unaided) respectively to 100% (aided). CONCLUSIONS: The long process of the incus is usually very hypoplastic in patients with ear atresia with a fused malleus-incus complex lateral to the stapes. VSB coupling to the long process of the incus or the stapes may be challenging in small mastoids. Coupling to the short process of the incus is comparatively a simple procedure, since there is no need for posterior tympanotomy and has no proximity to the facial nerve. The results of this study are similar to other ear atresia cases in the literature with classic FMT placement on the stapes or long process of the incus. Outcomes should be confirmed in a larger number of patients.

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OBJECTIVE: Cryptotia is one of the most common malformations of the upper auricle with aesthetic and functional consequences, however there is no standard treatment. We present the surgical technique and results of a kite flap procedure which can be used in the different cryptotia subtypes. METHODS: We reviewed all patients treated in our department from 2010 to 2015, using a mastoid fascia kite flap technique. The incision of this local flap follows the retro-auricular sulcus along the rim of the helix superiorly and drawing a skin paddle inferiorly. The mastoid fascia is exposed and a superiorly and posteriorly based flap is drawn and detached from the skull. Finally, the skin paddle is rotated and sutured between the superior helix and temporal skin creating the superior sulcus. The retro-auricular incision is closed directly inferiorly. RESULTS: Six patients (mean age 12) and seven ears were studied. One patient had bilateral cryptotia and only two had a normal contralateral ear. Mean follow-up was of 45 months. There was no skin necrosis, no complications reported and no revision surgery. CONCLUSIONS: We describe a reliable flap with a simple design and improved aesthetic result, as the thickness of the flap projects the helix well, the scar is entirely hidden in the retro-auricular sulcus and the direct suture induces a harmonious medialization of the inferior part of the ear and earlobe.

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Perrault syndrome (PS) is a rare autosomal recessive condition characterized by deafness and gonadic dysgenesis. Recently, mutations in five genes have been identified: C10orf2, CLPP, HARS2, HSD17B4, and LARS2. Probands included are presented with sensorineural deafness associated with gonadic dysgenesis. DNA was sequenced using next-generation sequencing (NGS) with a panel of 35 deafness genes including the five Perrault genes. Exonic variations known as pathogenic mutations or detected with <1% frequency in public databases were extracted and subjected to segregation analysis within each family. Both mutations and low coverage regions were analyzed by Sanger sequencing. Fourteen female index patients were included. The screening in four cases has been extended to four family members presenting with PS phenotype. For four unrelated patients (28.6%), causative mutations were identified: three homozygous mutations in C10orf2, CLPP, and HARS2, and one compound heterozygous mutation in LARS2. Three additional heterozygous mutations in LARS2 and HSD17B4 were found in three independent familial cases. All these missense mutations were verified by Sanger sequencing. Familial segregation analyses confirmed the molecular diagnosis in all cases carrying biallelic mutations. Because of NGS, molecular analysis confirmed the clinical diagnosis of PS in 28.6% of our cohort and four novel mutations were found in four Perrault genes. For the unsolved cases, exome sequencing should be performed to search for a sixth unknown PS gene.

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BACKGROUND: Oculo-auriculo-vertebral spectrum (OAVS) is a developmental disorder involving first and second branchial arches derivatives, mainly characterised by asymmetric ear anomalies, hemifacial microsomia, ocular defects and vertebral malformations. Although numerous chromosomal abnormalities have been associated with OAVS, no causative gene has been identified so far. OBJECTIVES: We aimed to identify the first causative gene for OAVS. METHODS: As sporadic cases are mostly described in Goldenhar syndrome, we have performed whole exome sequencing (WES) on selected affected individuals and their unaffected parents, looking for de novo mutations. Candidate gene was tested through transient knockdown experiment in zebrafish using a morpholino-based approach. A functional test was developed in cell culture in order to assess deleterious consequences of mutations. RESULTS: By WES, we identified a heterozygous nonsense mutation in one patient in the myelin transcription factor 1 (MYT1) gene. Further, we detected one heterozygous missense mutation in another patient among a cohort of 169 patients with OAVS. This gene encodes the MYT1. Functional studies by transient knockdown of myt1a, homologue of MYT1 in zebrafish, led to specific craniofacial cartilage alterations. Treatment with all-trans retinoic acid (RA), a known teratogenic agent causing OAVS, led to an upregulation of cellular endogenous MYT1 expression. Additionally, cellular wild-type MYT1 overexpression induced a downregulation of RA receptor ß (RARB), whereas mutated MYT1 did not. CONCLUSION: We report MYT1 as the first gene implicated in OAVS, within the RA signalling pathway.

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We discuss a case of severe respiratory depression in a child, with ultrarapid CYP2D6 genotype and obstructive sleep apnea syndrome, after taking tramadol for pain relief related to a day-case tonsillectomy.

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OBJECTIVE: To study gain and cutaneous tolerance of the Sophono Alpha1 implant, used for unilateral hearing rehabilitation in children with ear atresia, and to demonstrate non-inferiority compared to the referral closed skin device, BAHA® on a test-band. METHODS AND MATERIALS: Fifteen children included in a prospective clinical trial from September 2010 to November 2012. Tertiary care center. MAIN OUTCOMES: Pure tone and speech audiometry before surgery and at M6 and 12; Speech-in-noise tests with and without Alpha1 at M6. Quality of life questionnaire completed before surgery and at M6; children and parent's satisfaction assessed at M6. Cutaneous appearance assessed at M6, M12 and during the last clinical assessment. RESULTS: Patients' ages ranged from 61 to 129 months. They had a pure conductive deafness with a mean air conduction pure-tone average (ACPTA) of 69.02±9.31dB, and a mean SRT of 71.73±9.20dB. Follow-up was 12-32 months. At M6, the mean aided ACPTA was 33.49±4.89dB, the mean aided SRT 38.27±4.54dB and the mean aided SRT in noise was statistically improved (-7.80dB). Sophono Alpha1 demonstrated non-inferiority compared to BAHA® on a test-band. At M12, mean aided ACPTA was 2.94dB higher (p<0.001) but the mean SRT variation (+0.73dB) was not significantly different (p=0.35). At M12, all children used the implant 5 to 12h daily (mean: 10) without cutaneous complications. Both children and parents reported being satisfied or very satisfied. The score for 7/10 questions in silence or noisy environment was statistically improved when wearing the device. CONCLUSIONS: This prospective study demonstrate non inferiority, good cutaneous tolerance, satisfaction of children and parents and improvement of the quality of life with the Sophono Alpha1 compared to BAHA® on a test-band. In the light of this study and of the previously published series, the aided threshold is between that obtained with BAHA on a softband and percutaneous BAHA. The Sophono Alpha1 device needs to be part of the hearing solutions proposed for the hearing rehabilitation in children with ear atresia.

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OBJECTIVES/HYPOTHESIS: Vocal fold paralysis is the second most common congenital laryngeal anomaly in newborns. Bilateral paralysis is a severe condition and often remains of unknown etiology. We report our experience of congenital idiopathic bilateral vocal fold paralysis in newborns and infants, and discuss the therapeutic options. STUDY DESIGN: Retrospective review. METHODS: A retrospective review was carried out at a single tertiary referral center over a 15-year period of children presenting with congenital idiopathic bilateral laryngeal paralysis (CIBP). RESULTS: Twenty-six patients were identified and managed over period of the study (mean follow-up, 6.7 years). A tracheostomy was eventually performed in 14 patients, 12 during the neonatal period. Endoscopic treatment was performed in 16 patients and an external approach in five patients after endoscopic failure. Three patients were managed by watchful waiting. Spontaneous recovery occurred in 16 patients (median age, 14.5 months), including nine with a tracheostomy. Decannulation was achieved in 12 patients (median age, 42 months), and noninvasive positive pressure ventilation (NPPV) was applied in six patients. CONCLUSIONS: Only inhomogeneous series of pediatric bilateral laryngeal palsies have been published so far, making it difficult to identify prognostic and predictive markers, as well as therapeutic guidelines. Focusing on CIBP, our data suggest that the management strategy must take into account the possibility of a delayed spontaneous recovery. NPPV is an interesting therapeutic tool in this situation. A systematic somatic assessment is mandatory to look for associated conditions.

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OBJECTIVES: To assess the anatomic and functional outcome of underlay cartilage myringoplasty in children with cleft palate, at different postoperative periods compared with a patients-matched control group STUDY DESIGN: Case control study, tertiary referral center. METHODS: An otologic database was used to select children with cleft palate and perforated tympanic membrane who underwent myringoplasty between 1995 and 2012. These subjects were matched with control patients, without cleft palate, using the following criteria: age, size of perforation, status of contralateral ear, and status of middle ear mucosa. Charts were reviewed for the following: patients characteristics, preoperative findings, surgical data, postoperative anatomic and functional outcomes, and reinterventions. The postoperative findings were divided into 5 different periods. RESULTS: A group of 32 cleft palate patients as well as 32 control patients were included in this study, with a mean follow up of 63.6 ± 41 months. There were no differences between the groups in anatomic success as it was achieved in 84% in both groups. No differences were seen in functional outcome when compared with each different postoperative period. Using the last available audiogram, the postoperative mean air conduction and the air-bone gap were significantly worse in the cleft group compared with the control group, respectively, 26.1 ± 13.7 dB versus 18.4 ± 10.1 dB, p = 0.042; and 16.5 ± 9.4 dB and 11.3 ± 6.4 dB, p = 0.046. Additionally, the functional success was significantly worse in the cleft group; 58% versus 87% in the control group (OR, 5.5 [95% CI, 1.22-24.81], p = 0.027). CONCLUSION: Children with cleft palate can benefit from cartilage underlay myringoplasty in terms of closure of tympanic membrane, although there is a worse functional outcome.

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OBJECTIVES/HYPOTHESIS: This study aimed to report our experience in the management of congenital laryngeal stenosis and to compare our series and results to published data in the literature. STUDY DESIGN: Retrospective case series. Tertiary referral center for rare pediatric head and neck malformations. METHODS: Medical charts of patients diagnosed with congenital laryngeal stenosis in our institution were reviewed over a 15-year period, from 1996 to 2011. Surgical treatment consisted of an endoscopic procedure, open laryngeal surgery (OLS), or a combination of both. RESULTS: Sixteen patients met the inclusion criteria for the study and were divided in two groups: the endoscopic laryngoplasty (EL) group, with patients who underwent the endoscopic procedure as first-line treatment, and the OLS group, whose patients underwent open laryngoplasty with cartilage graft as first-line treatment. Each group contained eight patients with grade II to IV congenital stenosis. All patients, except one in the EL group, achieved a good result (<50% residual stenosis) at the end of the follow-up. CONCLUSIONS: This case series suggests that EL, with incision of the subglottic laryngeal cartilages with cold steel instruments and balloon dilation, is a safe and effective treatment for congenital laryngeal stenosis grade II to IV. This procedure could be considered as an alternative option to OLS, even as a first-line procedure. An endoscopic procedure does not preclude the possibility for an open laryngeal procedure in case of failure. A prolonged follow-up is mandatory. LEVEL OF EVIDENCE: 4.

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